ACTIVATED SKIN MAST-CELLS ARE INVOLVED IN MURINE HAIR FOLLICLE REGRESSION (CATAGEN)

Increasing evidence supports a role for mast cells (MC) in the control of tissue remodeling. Using the cyclic growth and regression activity of the murine hair follicle (HF) as a model, we have previously demon strated that MC are involved in regulating the HF transformation from resting (telogen) to active hair growth (anagen). In the present study , we investigated the potential role of skin MC in spontaneous HF regr ession (catagen), a rapid and highly controlled process of organ invol ution characterized by massive epithelial cell apoptosis. By histochem istry, immunohistochemistry, and electron microscopy, we first assesse d the number, location, and granulation status of perifollicular MC du ring the anagen-catagen-telogen transformation of back skin HF. Sponta neous catagen induction was associated with a dramatic reduction of de rmal MC numbers, preceded by an increase in the percentage of degranul ated MC. In vivo, the MC-secretagogues substance P and adrenocorticotr opic hormone induced premature and dystrophic catagen development in a nagen HF, whereas inhibitors of MC degranulation retarded normal catag en development. Comparing HF cycling in MC-deficient WBB6F(1)-Kit(W)/K it(Wv) and congenic normal (+/+) mice, catagen development was retarde d in the virtual absence of MC. These data support the notion that MC function as hair cycle regulators and are involved in the control of H F regression. The mouse model employed here offers an excellent tool f or dissecting the physiologic role of MC as ''central switchboards of tissue remodeling'' in developmentally regulated systems, specifically in organ involution processes.